Current Pharmaceutical Design - Volume 27, Issue 35, 2021

Long non-coding RNAs (lncRNAs) are functionally versatile molecules that regulate gene expression at all levels of biological organization. RNA modulation, at the moment, has emerged as a powerful therapeutic technique to treat human diseases. Lately, lncRNAs have been acknowledged as key players in human metabolism and, indeed, implicated in the etiology of many common diseases other than cancers, where they can perhaps serve as reliable markers to determine disease status or assess outcomes of an intervention. Here, in this review, we cite examples of such lncRNAs, discuss their mechanistic role in human diseases and their genetic association, quote potential biomarkers found in human blood, summarize the methods for therapeutic targeting lncRNAs and examine the progress of lncRNA based drugs in clinical trials. Thus, we propose that lncRNAs serve as both a biomarker and an effective therapeutic target with promising clinical utility to manage human metabolic diseases.

Breast cancer is the most common type of malignancy affecting women worldwide and also stands being the most diagnosed one. Mammography is considered as the golden standard for diagnosis but there are high chances that it can give false- negative as well as false-positive test results. Finding cost-effective, readily available diagnosis along with increased sensitivity as well as specificity is the need right now to decrease the mortality as well as the morbidity rate. The application of biomarkers to clinical use has paved the way for a better prognosis, diagnosis, detection, screening and better clinical results. The efficacy of the treatment is enhanced. Biomarkers are known to cause an advancement in breast cancer study and are expected to improve the quality of life in patients. Not only tissue biomarkers but serum and circulating biomarkers are also of significance in patients. This review highlights the particulars about the current use and application of biomarkers in an effective prognosis, detection, treatment of the breast cancer and also the ones which are currently being studied under clinical trials and have the potential to be advantageous and more specific in the future.

Background: Inflammatory bowel disease (IBD) is a multifactorial condition influenced by the immune system, the intestinal microbiota, environmental factors, genetic and epigenetic factors. Genetic- and environment- induced dysregulation of the Nuclear Factor-kappa B (NF-ΚB) transcription factor pathway has been linked to IBD pathogenesis. Objective: To assess the current evidence in relation to the contribution of the classical and alternative NF-ΚB pathways in IBD and to discuss the epigenetic mechanisms that impact on NF-ΚB function. Methods: A Medline search for ‘NF-kappaB/NF-ΚB’, in combination with terms including ‘inflammatory bowel disease/IBD’, 'intestinal inflammation', ‘Crohn's disease’, ‘ulcerative colitis’, 'colitis'; ‘epigenetics’, ‘DNA methylation’, ‘histones’, ‘microRNAs/miRNAs’ and ‘short non-coding/long non-coding RNAs’ was performed. Results: Both NF-ΚB pathways contribute to the chronic inflammation underlying IBD by regulating the inflammatory immune responses and homeostasis of the intestinal epithelium (classical pathway) or regulating bowel inflammation and epithelial microfold (M) cell function (alternative pathway). DNA methylation is a common epigenetic modification in intestinal inflammation, including NFKB1 and RELA loci. Conversely, little is understood regarding epigenetic effects on genes encoding other NF-ΚB subunits, particularly those of the alternative pathway, and in the context of IBD. However, NF-ΚB interaction with chromatin modifiers is also seen to be an essential mechanism of regulation of downstream target genes relevant to NF-ΚB-mediated inflammatory responses. Conclusion: Further research is clearly warranted in this area, as understanding the cell-specific regulation of the NF-ΚB pathways will bring researchers into a position to achieve more efficient stratification of IBD patients, and more targeted and effective choice of treatment.

Extracellular vesicles (EVs, formerly known as exosomes) are small, extracellular membrane-bound particles that play a role in cellular communication via transporting different cargos, including proteins, DNAs, RNAs, etc. Their role has been shown in different endocrine/paracrine signaling in different organs, such as the cardiovascular system. Currently, mortality and morbidity rates caused by cardiovascular disease (CVD) have become an important issue among healthcare systems all over the world. EVs great potentials for clinical diagnosis and treatment offer a bright future in assessing different types of CVDs. In this review, we have summarized the variable roles of these nano-sized biological membrane-enclosed vesicles in myocardial injury, repair, and regeneration. We have also reviewed the value of EVs as diagnostic and prognostic biomarkers in cardiology medicine and emphasized the promising capabilities of EVs as natural drug-delivery vehicles as a novel targeting treatment.

Hypertension is a common chronic disease that particularly affects the elderly and can trigger several cardiovascular conditions. Although the treatment of hypertension has evolved in recent decades, many hypertensive patients still do not have properly controlled blood pressure. Accumulating evidence supports the hypothesis that DNA methylation plays an important role in regulating gene expression, altering the phenotype and function of the cardiovascular system. The present review highlights recent advances in research on DNA methylation in the development of hypertension. Several preclinical and clinical evidence show that methylation of different targets appears to be involved in hypertension. Studies of the involvement of DNA methylation have greatly improved our understanding of hypertension, but its use as a valid therapeutic target is still unknown. Further studies could help to bring to light the truth about gene therapy in hypertension.

Background: Metabolic syndrome is a clinical condition that deserves special attention because it puts the individual at high cardiovascular risk, especially heart attack and stroke. Considering precision medicine, it would be advisable to evaluate the individual cardio-metabolic risk by estimating the coexistence of risk factors (abdominal obesity, low level of High-Density Lipoprotein Cholesterol, High Triglycerides, and small dense Low-Density Lipoproteins sub-classes, hypertension, and elevated fasting glycemia), which could engrave on metabolism increasing cardiovascular mortality. Objective: To identify genetic and epigenetic biomarkers may assist in the possibility of helping follow-up strategies and other measures of prevention and in metabolic risk. Methods: We searched for studies that valued the combination between epigenetic biomarkers and all factors of cardio-metabolic risk. Results: Numerous researches have investigated the molecular start of metabolic alterations, focusing on the epigenetic mark, as methylation of DNA, histone modifications and non.coding RNAs. It has been found that DNA methylation is the most searched epigenetic sign in the human genome concerning the control of gene expression. Conclusion: For the screening, diagnosis, and prognosis of metabolic syndrome and the prescription of personalized medicine, the DNA methylation biomarkers specify for subjects have been recognized as an ensuring tool. While these results are promising, further investigations are needed to unravel the complicated synergic association of the genome, epigenome and the situations related to metabolic pathology.

Background: Molecular genetic mechanisms, signaling pathways, conditions, factors, and markers of the osteogenic differentiation of mesenchymal stem cells (MSCs) are being actively studied and are among the most studied areas in the field of cellular technology. This attention is largely due to the mounting contradictions in the seemingly classical knowledge and the constant updating of results in the analyzed areas. In this regard, we focus on the main classical concepts and some new factors and mechanisms that have a noticeable regulatory effect on the differentiation potential of postnatal MSCs. Results: This review considers the importance of the sources of MSCs for the realization of their differentiation potential, molecular genetic factors and signaling pathways of MSC differentiation, the role of inflammatory cytokines and chemokines in osteogenesis, biomechanical signals, and the effect of conformational changes in the cellular cytoskeleton on MSC differentiation. Conclusion: It is concluded that it is necessary to move from studies focused on the effects of local genes to those taking multiple measurements of the gene-regulatory profile and the biomolecules critical for the implementation of numerous, incompletely studied osteogenic factors of endogenous and exogenous origin. Among the cornerstones of future (epi)genetic studies, whether osteomodulatory effects are realized through specific signaling pathways and/or whether cross-signaling with known genes drives the osteogenic differentiation of MSCs remains to be determined.